Method to prevent and treat osteoarthritis by calcium channel blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers

Abstract

A method is provided to prevent and to treat Osteoarthritis syndrome by using Calcium Channel Blockers, Angiotensin-Converting Enzyme (ACE) Inhibitors, or Angiotensin Receptor Blockers (ARB), and more particularly, to a method to prevent and treat Osteoarthritis syndrome by using Calcium Channel Blockers, Angiotensin-Converting Enzyme Inhibitors, or Angiotensin Receptor Blockers that are not taken orally, but administered by intra-articular injection into the affected joint or administered by topical application to the skin in a region of the affected joint, so as to increase the capillary network and articular blood supply to the joint or to increase hyaluronic acid production to the articular cartilage, bones, articular ligaments, synovia tissue and other soft tissues.

What is claimed is: 
     
         1 . A pharmaceutical composition for the treatment of osteoarthritis syndrome, comprising:
 at least one vasodilator; and   at least one pharmaceutical excipient.   
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition is in a form adapted for topical administration or intra-articular injection to an affected joint. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the form is selected from the group consisting of an oil, a liquid and a suspension for topical application on the skin in the region of an affected joint. 
     
     
         4 . The pharmaceutical composition  claim 1 , wherein the pharmaceutical composition is formulated as a liquid or a suspension of the at least one vasodilator, wherein the vasodilator is a contact vasodilator. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the vasodilator is a calcium channel blocker. 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the at least one calcium channel blocker is a dihydropyridine selected from the group consisting of nifedipine, isradipine, felodipine, amlodipine, nicardipine, and clevidipine. 
     
     
         7 . The pharmaceutical composition of  claim 5 , wherein the at least one calcium channel blocker is a non dihydropyridine selected from the group consisting of verapamil and diltiazem. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the vasodilator is an ACE inhibitor selected from the group consisting of benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril. 
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein the vasodilator is an angiotensin receptor blocker selected from the group consisting of azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the vasodilator is a nitrate selected from the group consisting of nitroglycerin, isosorbide mononitrate and isosorbide dinitrate. 
     
     
         11 . The pharmaceutical composition of  claim 1 , wherein the vasodilator is an alpha blocker selected from the group consisting of doxazosin, prazosin, and terazosin. 
     
     
         12 . The pharmaceutical composition of  claim 1 , wherein the vasodilator is a beta blocker selected from the group consisting of acebutolol, atenolol, bisoprolol fumarate, carvedilol, esmilol, labetalol, metoprolol tartrate, metoprolol succinate, nadolol, nebivolol, penbutolol sulfate, propranolol, sotalol, hydrochlorothiazide, and bisoprolol. 
     
     
         13 . The pharmaceutical composition of  claim 1 , wherein the vasodilator is hydralazine. 
     
     
         14 . The pharmaceutical composition of  claim 1 , wherein the vasodilator is an angiotensin receptor-neprilysin inhibitor. 
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the angiotensin receptor-neprilysin inhibitor is sacubitril/valsartan. 
     
     
         16 . The pharmaceutical composition of  claim 1 , wherein the concentration of the vasodilator is about 0.0001 mg per ml to 1000 mg per ml, optionally 1 mg per ml to 10 mg per ml, optionally 1 mg per ml to 1000 mg per ml, optionally 5 mg per ml to 10 mg per ml, optionally 10 mg per ml, optionally 20 mg per ml, optionally 30 mg per ml, optionally 60 mg per ml, optionally 90 mg per ml, optionally 120 mg per ml, optionally 180 mg per ml, optionally 240 mg per ml. 
     
     
         17 . A method for the treatment of osteoarthritis syndrome in a patient in need thereof, comprising:
 administering an effective amount of the pharmaceutical composition according to  claim 1  to a patient in need thereof.   
     
     
         18 . The method of  claim 17 , for the treatment or prophylaxis of osteoarthritis syndrome in a knee. 
     
     
         19 . The method of  claim 17 , for the treatment or prophylaxis of osteoarthritis syndrome in a joint other than a knee. 
     
     
         20 . The method of  claim 17 , wherein the composition is administered once a day, optionally two or more times a day, optionally once a week, optionally two or more times a week, optionally once a month, optionally two or more times a month, optionally a plurality of times a year.